The role of the cyclic nucleotides, cAMP and cGMP, in ganglia is being studied. It has been established that cAMP is not involved in the blockade of ganglionic transmission by adrenergic drugs. A beta receptor system is coupled to adenylate cyclase in rat sympathetic ganglia and accounts for the marked increase in cAMP of ganglia treated with isoproterenol. Of current interest is the study of K ion-induced stimulation of cGMP formation in rat ganglia. K ion causes a 50-80 fold increase in cGMP that requires Ca ions and intact preganglionic nerves. The response to K ion is unaffected by atropine, hexamethinium or physostigmine. The results suggest that K ion releases a transmitter to activate guanylate cyclase or that guanylate cyclase activity resides in the preganglionic nerve terminals. Stimulation of guanylate cyclase by NaN3 does not require (Ca ions)o. Future experiments will be designed to study the role of cGMP in nerve terminals and ganglion cells.